Early Methicillin-resistant Staphylococcus Aureus (MRSA) Therapy in Cystic Fibrosis (CF)

Cystic Fibrosis Clinical Trial

— STAR-Too  

Official title:

Early MRSA Therapy in CF - Culture Based vs. Observant Therapy (Treat or Observe) (Star-TOO - STaph Aureus Resistance - Treat or Observe)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01349192
• Other study ID #: STAR-too-10K0
• Status: Completed
• Phase: Phase 2
• First received: May 4, 2011
• Last updated: February 10, 2016
• Start date: April 2011
• Est. completion date: December 2015

Study information

• Verified date: February 2016
• Source: University of North Carolina, Chapel Hill
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Purpose: There has been a recent, rapid increase in prevalence of Methicillin-resistant Staphylococcus aureus (MRSA) among patients with Cystic Fibrosis (22% across US CF centers in 2009). Some epidemiologic studies suggest possible worse outcomes, a recent analyses showing this with chronic but not intermittent MRSA. Given the chronic difficult to treat lung infections in CF it is unclear how the onset of MRSA should be approached. This randomized, controlled, interventional study seeks to determine if an early eradication protocol is effective for eradication of MRSA and will provide an opportunity to obtain data regarding early clinical impact of new isolation of MRSA.

Participants: Cystic fibrosis patients with new isolation of MRSA from their respiratory culture on a routine clinic visit.

Procedures (methods): Randomized, open-label, multi-center study comparing use of an eradication protocol to an observational group who receives the current standard of care i.e. treatment for MRSA only with pulmonary exacerbations.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: December 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 4 Years to 45 Years

Eligibility

Inclusion Criteria:

1. Male or female = 4 and = 45 years of age at the Screening Visit.

2. Documentation of a CF diagnosis as evidenced by one or more clinical features consistent with the CF phenotype and one or more of the following criteria:

• sweat chloride = 60 mEq/liter by quantitative pilocarpine iontophoresis test (QPIT)

• two well-characterized mutations in the cystic fibrosis transmembrane conductive regulator (CFTR) gene

• Abnormal nasal potential difference (change in NPD in response to a low chloride solution and isoproteronol of less than -5 mV)

3. First OR early repeat MRSA colonization defined as:

• First MRSA colonization: first documented isolation of MRSA from respiratory tract occurred = 6 months prior to screening

• OR Early repeat MRSA colonization:

MRSA was previously isolated from the respiratory tract (= 2 times), but this was followed by at least 1 year of documented negative cultures for MRSA as noted below:

-- At least 2 cultures performed at least 3 months apart to document 1 year of culture negativity. Each of these cultures should be documented to have been collected at least 1 week after end of any antibiotic prescription with MRSA activity.

Patient again recently positive for MRSA from the respiratory tract (within 6 months prior to screening)

4. Clinically stable with no significant changes in health status within the 14 days prior to screening

5. Written informed consent (and assent when applicable) obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study

A repeat culture from the respiratory tract is obtained at screening but does not have to be positive to be able to enter the study.

Exclusion Criteria:

1. Received antibiotics with activity against MRSA within 28 days prior to screening (see study manual for list of antibiotics)

2. Use of an investigational agent within 28 days prior to screening

3. For subjects = 6 years of age: FEV1 at screening < 30% of predicted for age based on the Wang (males < 18 years, females < 16 years) or Hankinson (males = 18 years, females = 16 years) standardized equations

4. MRSA from the screening culture resistant to rifampin OR resistant to both TMP/SMX and minocycline

5. History of intolerance to oral rifampin, or topical chlorhexidine or mupirocin

6. History of intolerance to both TMP/SMX and minocycline

7. < 8 years of age and either allergic or intolerant to TMP/SMX or screening MRSA resistant to TMP/SMX

8. = 8 years of age and allergic or intolerant to TMP/SMX and screening MRSA resistant to minocycline

9. = 8 years of age and allergic or intolerant to minocycline and screening MRSA resistant to TMP/SMX

10. For females of child bearing potential: pregnant, breastfeeding, or unwilling to use barrier contraception through Day 15 of the study

11. Abnormal renal function at Screening, defined as estimated creatinine clearance <50 mL/min using the Cockcroft-Gault equation

12. Abnormal liver function at the time of screening, defined as =2x upper limit of normal (ULN), of serum aspartate transaminase (AST) or serum alanine transaminase (ALT)

13. History of solid organ or hematological transplantation

14. Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis
• Methicillin-resistant Staphylococcus Aureus
• Staphylococcal Infections

Intervention

Drug:
• Rifampin
Adult Dose: 300mg twice daily for 14 days. Pediatric Dose: <40kg : 15mg/kg daily for 14 days divided every 12 hours.
• Trimethoprim/Sulfamethoxazole
Adult Dose: 320/1600 orally twice daily for 14 days. Pediatric Dose: <40 kg : 8mg/kg trimethoprim / 40 mg/kg sulfamethoxazole twice a day for 14 days.
• Minocycline
only subjects greater or equal to 8 years of age, who are not able to tolerate TMP/SMX or whose screening MRSA is resistant to TMP/SMX should be prescribed minocycline. Adult dose: 100 mg orally twice daily for 14 days Pediatric dose: < 50 kg : 2mg/kg orally twice daily for 14 days not to exceed 200mg per day.
• Mupirocin
1 gram 2% nasal ointment generously applied to each nostril using a cotton swab twice daily for 14 days.
• chlorhexidine gluconate oral rinse
for subjects able to swish without swallowing. 0.12% chlorhexidine gluconate oral rinse twice daily for 14 days.
• 2% Chlorhexidine solution wipes
whole body wash solution wipes once daily for first 5 days.

Behavioral:
• Environmental Decontamination
wipe down high touch surfaces and medical equipment with surface disinfecting wipes daily for the first 21 days. wash all linens and towels in hot water once weekly for three weeks.

Locations

Country	Name	City	State
United States	University of Michigan Health System	Ann Arbor	Michigan
United States	The Children's Hospital	Aurora	Colorado
United States	The Children's Hospital-University of Birmingham	Birmingham	Alabama
United States	N.C Memorial Hospital and N.C Children's Hospital	Chapel Hill	North Carolina
United States	CFF Care Center & Pediatric Program Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	University of Florida	Gainesville	Florida
United States	Baylor College of Medicine	Houston	Texas
United States	Children's Hospitals and Clinics of Minnesota Minneapolis	Minneapolis	Minnesota
United States	Seattle Children's	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington
United States	St. Louis Children's Hospital	St. Louis	Missouri

Sponsors (14)

Lead Sponsor

Collaborator

University of North Carolina, Chapel Hill

Baylor College of Medicine, CF Therapeutics Development Network Coordinating Center, Children's Hospital Medical Center, Cincinnati, Cook Children's Medical Center, Seattle Children's Hospital, St. Louis Children's Hospital, University of Alabama at Birmingham, University of Colorado, Denver, University of Florida, University of Michigan, University of Texas Southwestern Medical Center, University of Washington, Washington University School of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Microbiology	Proportion of subjects in each arm with MRSA negative respiratory cultures at day 28.	Day 28	No
Secondary	Antibiotic Use	proportion of subjects treated with oral, inhaled, and IV antibiotics over the 6 month study and number of days of use.	6 months	No
Secondary	Exacerbation	Proportion of subjects with a protocol defined pulmonary exacerbation between baseline and day 28 who are treated with antibiotics active against MRSA.	6 months	No